The primary activity of the contract will be to evaluate (i) therapeutic approaches and (ii) inhibitors of mucosal transmission alone and in combination. The term "therapeutic approaches" includes, but is not limited to, the following: antiviral agents (drugs and biologics), immune-based strategies, and gene-based therapy. The term "transmission inhibitor" includes drug-based, immune-based, biologics, and natural product inhibitors of sexual transmission. Excluded from these studies is prophylactic vaccine-based suppression of viral transmission. Evaluation encompasses the determination of efficacy and toxicity and when needed, limited pharmacokinetics. Model development will continue to be an integral part of this program only with respect to improving existing models.